AGA clinical practice update: Expert review
Management of Clostridium difficile Infection in Inflammatory Bowel Disease: Expert Review from the Clinical Practice Updates Committee of the AGA Institute

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The purpose of this expert review is to synthesize the existing evidence on the management of Clostridium difficile infection in patients with underlying inflammatory bowel disease. The evidence reviewed in this article is a summation of relevant scientific publications, expert opinion statements, and current practice guidelines. This review is a summary of expert opinion in the field without a formal systematic review of evidence.

Best Practice Advice 1: Clinicians should test patients who present with a flare of underlying inflammatory bowel disease for Clostridium difficile infection.

Best Practice Advice 2: Clinicians should screen for recurrent C difficile infection if diarrhea or other symptoms of colitis persist or return after antibiotic treatment for C difficile infection.

Best Practice Advice 3: Clinicians should consider treating C difficile infection in inflammatory bowel disease patients with vancomycin instead of metronidazole.

Best Practice Advice 4: Clinicians strongly should consider hospitalization for close monitoring and aggressive management for inflammatory bowel disease patients with C difficile infection who have profuse diarrhea, severe abdominal pain, a markedly increased peripheral blood leukocyte count, or other evidence of sepsis.

Best Practice Advice 5: Clinicians may postpone escalation of steroids and other immunosuppression agents during acute C difficile infection until therapy for C difficile infection has been initiated. However, the decision to withhold or continue immunosuppression in inflammatory bowel disease patients with C difficile infection should be individualized because there is insufficient existing robust literature on which to develop firm recommendations.

Best Practice Advice 6: Clinicians should offer a referral for fecal microbiota transplantation to inflammatory bowel disease patients with recurrent C difficile infection.

Section snippets

Methods

This article is not based on a formal systematic review but instead seeks to provide practical advice based on the best available evidence, including existing clinical studies, systematic reviews, and practice guidelines. The focus is on the management of both CDI and IBD in patients with underlying IBD who are infected by CDI.

Epidemiology of Clostridium difficile Infection in Inflammatory Bowel Disease

In the late 1970s, toxigenic C difficile was identified as a causative agent in antibiotic-associated colitis and pseudomembranous colitis.3, 4 Shortly thereafter, an increased risk for colonization with toxin-producing C difficile was noted in individuals with IBD, leading to an active debate as to whether C difficile toxins may be a cause for IBD or IBD flares.11 In more recent years, as the incidence and severity of CDI has increased in the general population, even greater increases have

Pathogenic Mechanisms

The potential first step in the pathogenesis of CDI consists of disruption of the normal colonic bacterial populations by antibiotic therapy (Figure 3).1, 18 This interferes with the colonization resistance against CDI that naturally is conferred by the gut microbiome. If exposure to C difficile spores then occur, as is common in nosocomial settings, colonization and disease can follow. CDI risk is age-related; the rate of infection is 7-fold higher in persons older than age 65 years compared

Disease Outcomes

The combination of CDI and IBD is associated with an increased risk for multiple adverse outcomes when compared with either condition alone (Table 2). Patients with both CDI and IBD remain in the hospital for 3 days longer (95% confidence interval, 2.3–3.7 d) than those IBD patients who are not infected.16 Concomitant CDI and IBD patients are less likely to respond to medical therapy for their CDI.15, 16, 30 These patients are susceptible to frequent flares of their underlying IBD associated

Clinical Presentation and Diagnosis

The clinical presentations of CDI and of IBD with colitis overlap substantially. Diarrhea is the most prominent symptom, but is more likely to be bloody in IBD; other shared symptoms include abdominal discomfort and fever. Hence, clinical differentiation between an acute IBD flare and acute CDI complicating IBD is difficult. All patients with IBD who present with worsening of underlying diarrhea or symptoms or signs suggesting a colitis flare such as increased blood in stool should be tested

Management of Clostridium difficile Infection in Inflammatory Bowel Disease

Management of CDI in IBD is exceptionally challenging with dilemmas including distinguishing symptoms of an active infection from an IBD flare, the choice of antibiotic therapy for CDI, and timing and need for escalation vs de-escalation of immunosuppressants for IBD. There is emerging evidence for the use of fecal microbiota transplantation (FMT) for the management of CDI in IBD. In the absence of prospective data specific for the treatment of CDI in IBD patients, evidence from the non-IBD

Immunosuppression in the Management of Clostridium difficile Infection in Inflammatory Bowel Disease

The biggest challenge in the management of CDI in IBD remains distinguishing symptoms of an IBD flare from those of superimposed CDI. Furthermore, immunosuppression may lead to worsening of the underlying infection but may be required to manage the IBD flare caused by CDI. As a result, the decision to augment immunosuppressive therapy for clinical worsening secondary to suspected IBD requires careful judgment. In clinical practice, CDI in patients with IBD frequently is treated with both

Summary and Conclusions

C difficile is a common complication in patients with IBD (Table 3). Clinicians should test all patients who present with a flare of underlying IBD for CDI. Patients should be tested for recurrent CDI if diarrhea or other symptoms of colitis persist or return after antibiotic treatment. IBD patients with CDI should be treated with vancomycin instead of metronidazole. Inflammatory bowel disease patients with CDI who have profuse diarrhea, severe abdominal pain, a markedly increased peripheral

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    This article has an accompanying continuing medical education activity, also eligible for MOC credit, on page e60. Learning Objective–Upon completion of this activity, successful learners will be able to identify and manage Clostridium difficile infection in patients with inflammatory bowel disease.

    Reprint requests Address requests for reprints to: Chair, Clinical Practice Updates Committee, AGA Institute, 4930 Del Ray Avenue, Bethesda, Maryland 20814. e-mail: [email protected]; fax: (301) 652-3890.

    Conflicts of interest These authors disclose the following: Sahil Khanna serves as a consultant to Rebiotix, Inc, and Summit Pharmaceuticals; and Ciarán P. Kelly serves as a consultant to Merck, Inc, Seres Therapeutics, Summit Pharmaceuticals, and Takeda Pharmaceuticals. The remaining author discloses no conflicts.

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